Amphiphilic block copolymers that can form a core-shell type micelle in an aqueous medium have been used for delivering hydrophobic drugs such as anti-cancer drugs, adriamycin and paclitaxel, the drug being loaded in the hydrophobic core and the hydrophilic shell enhancing the solubilization of the micelle.
Such a micelle having a size of not more than 200 nm and a polyethyleneoxide hydrophilic shell is neither easily destroyed by the reticuloenthelial or mononuclear phagocyte system nor excreted through kidney, and therefore, circulates in a living body for a long period of time, accumulating at the blood vessel around tumors where the transfer of materials is much enhanced and more selective than that around normal cells.
The hydrophobic block of such amphiphilic block copolymers may be divided into two groups, i.e., (i) a hydrophobic block having no functional group, e.g. polylactide, polycarprolactone, poly(lactide-glycolide), poly(β-benzyl L-aspartate), as way disclosed in Korean Patent Publication Nos. 1999-69033 and 2001-105439, European Patent Publication No. 583055, U.S. Pat. No. 6,322,805 and Japanese Patent Publication No. 1994-206815, and (ii) a hydrophobic block having a plurality of functional groups, e.g., poly(β-substituted aspartate), poly(γ-substituted glutamate), poly(L-leucine), described in European Patent Publication No. 583955. In case the hydrophobic block has no functional group, the drug loading capacity of the hydrophobic core is limited, whereas when contains too much functional groups, for example, 300 or more per hydrophobic block, the amphiphilic nature of the copolymer is lost and dissolves in an aqueous medium and cannot form a micelle. Therefore, the step of chemically bonding a hydrophobic drug to such copolymer has been performed to prepare a delivery composition.
Accordingly, in order to solve this problem and increase the drug loading capacity and sustained-release characteristics of micelle drug composition, there has been a need to develop amphiphilic block copolymeric micelles containing a small quantity of functional groups in a hydrophobic block.